title: Targeting urocortin signaling pathways to enhance cardioprotection: is it time to move from bench to bedside?
abstract: Despite the exponential growth in medical knowledge, cardiovascular diseases (CVDs) contribute to more than one-third of worldwide morbidity and mortality. A range of therapies already exist for established CVDs, although there is significant interest in further understanding their pathogenesis. The urocortins (Ucns) are peptide members of the corticotrophin-releasing factor family, a group of evolutionary conserved peptides with homologues in fish, amphibians and mammals and considered to play a pivotal role in energy homeostasis and local tissue repair. A number of preclinical studies in vitro, in-vivo and ex-vivo have defined a multifaceted effect of Ucns on the cardiovascular system. Different G-protein coupled signaling and protein-kinase pathways have been shown to be activated by Ucns, together with different transcriptional and translational effects, all of which preferentially converge on the mitochondria, where the modulation of apoptosis is considered their principal action. It has been demonstrated in experimental models, and consequentially suggested in human diseases, that Ucn-mediated inhibition of apoptosis can be exploited for the improvement of both therapeutic and preventative strategies against CVDs. Specifically, some unavoidable iatrogenic ischemia/reperfusion (I/R) injuries, e.g. during cardiac surgery or percutaneous coronary angioplasty, may greatly benefit from the anti-apoptotic effect of Ucns. However, few studies on the topic have been employed in humans to date. Therefore, this review will focus on the different intra-cellular mechanisms of action of Urocortins, and detail the different Ucn-mediated pathways identified so far. It will also highlight the limited evidence already existing in human clinical and surgical settings, as well as emphasize the potential uses of Ucns in human cardiac pathology.
authors.affiliation: Division of Cardiac Surgery, University of Verona Medical School, Verona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Onorati
authors.forename: Carol
authors.initials: C
authors.lastname: Chen-Scarabelli
authors.forename: Richard
authors.initials: R
authors.lastname: Knight
authors.forename: Anastasis
authors.initials: A
authors.lastname: Stephanou
authors.forename: Bibhu
authors.initials: B
authors.lastname: Mohanti
authors.forename: Francesco
authors.initials: F
authors.lastname: Santini
authors.forename: Maddalena
authors.initials: M
authors.lastname: Tessari
authors.forename: Annapoorna
authors.initials: A
authors.lastname: Kini
authors.forename: Jagat
authors.initials: J
authors.lastname: Narula
authors.forename: Louis
authors.initials: L
authors.lastname: Saravolatz
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mazzucco
authors.forename: Tiziano
authors.initials: T
authors.lastname: Scarabelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Faggian
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D015398:Signal Transduction; D054832:Urocortins / Q000378:metabolism*
chemical_list: D054832:Urocortins